The field of research that deals with treatment of certain diseases involving immune therapy can be termed as Immunotherapeutics. The method involves treatment of disease by inducing, enhancing, or suppressing an immune response. Immunotherapies that are designed to elicit or amplify an immune response can be classified as activation immunotherapies, while immunotherapies that reduce or suppress immune responses are termed as suppression immunotherapies

Immunotherapeutic agents use or modify immune mechanisms. Use of these agents is rapidly evolving; new classes, new agents, and new uses of current agents are certain to be developed. A number of different classes of immunotherapeutic agents have been developed

• Monoclonal antibodies
• Fusion proteins
• Soluble cytokine receptors
• Recombinant cytokines
• Small-molecule mimetics
• Cellular therapies

Monoclonal antibodies

Monoclonal antibodies (mAbs) are manufactured in vitro to recognize specific targeted antigens (Ags); they are used to treat solid and hematopoietic tumors and inflammatory disorders. The monoclonal antibodies that are currently in clinical use include

• Murine
• Chimeric
• Humanized
• Fully human

Fusion proteins

These hybrid proteins are created by linking together the gene sequences encoding all or part of 2 different proteins to generate a chimeric polypeptide that incorporates desirable attributes from the parent molecules (eg, a cell-targeting component combined with a cell toxin). The circulating half-life of therapeutic proteins can also often be improved by fusing them to another protein that naturally has a longer serum half-life (eg, the Fc region of IgG).

Soluble cytokine receptors

Soluble versions of cytokine receptors are used as therapeutic reagents. They can block the action of cytokines by binding with them before they attach to their normal cell surface receptor.

Etanercept, a fusion protein, consists of 2 identical chains from the CD120b receptor for tumor necrosis factor (TNF)-alpha. This agent thus blocks TNF-alpha and is used to treat rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.

Soluble interleukin (IL) receptors (eg, those for IL-1, IL-2, IL-4, IL-5, and IL-6) are being developed for treatment of inflammatory and allergic disorders and cancer.

Recombinant cytokines

Colony-stimulating factors (CSF), such as erythropoietin, granulocyte CSF (G-CSF), and granulocyte-macrophage CSF (GM-CSF), are used in patients undergoing chemotherapy or transplantation for hematologic disorders and cancers and in patients with severe chronic neutropenia (see table Some Immunotherapeutic Agents in Clinical Use). Interferon-alpha (IFN-alpha) and IFN-gamma are used to treat cancer, immunodeficiency disorders, and viral infections; IFN-beta is used to treat relapsing multiple sclerosis. Many other cytokines are being studied.

Anakinra, used to treat rheumatoid arthritis, is a recombinant, slightly modified form of the naturally occurring IL-1R antagonist; this drug attaches to the IL-1 receptor and thus prevents binding of IL-1, but unlike IL-1, it does not activate the receptor.

Cells expressing cytokine receptors can be targeted by modified versions of the relevant cytokine (eg, denileukin diftitox, which is a fusion protein containing sequences from IL-2 and from diphtheria toxin). Denileukin is used in cutaneous T-cell lymphoma to target the toxin to cells expressing the CD25 component of the IL-2 receptor.

Small-molecule mimetics

Small linear peptides, cyclicized peptides, and small organic molecules are being developed as agonists or antagonists for various applications. Screening libraries of peptides and organic compounds can identify potential mimetics (eg, agonists for receptors for erythropoietin, thrombopoietin, and G-CSF).

Cellular therapies

Immune system cells are harvested (eg, by leukapheresis) and activated in vitro before they are returned to the patient. The aim is to amplify the normally inadequate natural immune response to cancer. Methods of activating immune cells include using cytokines to stimulate and increase numbers of antitumor cytotoxic T cells and using pulsed exposure to antigen-presenting cells such as dendritic cells with tumor antigens. Before being returned to the patient, T cells can be genetically engineered to express chimeric antigen receptors (CAR) or T cell receptors (TCR) capable of recognizing tumor antigens, an approach that has shown efficacy in patients with leukemia sand lymphoma.

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John Kimberly
Assistant Editorial Manager
Journal of Vaccines & Vaccination
Email: jvv@scholarlypub.com